The present invention relates to a fluorescence diagnosis system.
Such a fluorescence diagnosis system is used, for example, for what is called photodynamic diagnosis of tumors. In photodynamic diagnosis, a patient is administered a suitable tumor marker substance, for example 5-aminolevulinic acid (5-ALA). 5-ALA is a precursor in heme biosynthesis. 5-ALA collects in tumor tissue and causes a fluorescence that can be excited with a specific wavelength. Areas in which 5-ALA has collected, that is to say tumorous areas, fluoresce in a red color. Since blue light is used as the excitation light, this can be filtered out in the observed view, and the tumorous areas thus stand out clearly from the healthy tissue.
It is also known that healthy tissue fluoresces at certain wavelengths of the excitation light even without addition of a marker. This phenomenon is referred to as autofluorescence. Tumor tissue, by contrast, hardly fluoresces at all. It appears dark in contrast to the surrounding healthy tissue and can in this way be distinguished from the healthy tissue.
This phenomenon too can be used to distinguish fluorescing tumor cells from surrounding healthy tissue. This autofluorescence, however, is generally much weaker than the fluorescence generated by a tumor marker, so that this form of diagnosis has a somewhat less important role.
Systems for photodynamic diagnosis, for example for early detection of bladder carcinoma, are marketed by the Applicant and are described, inter alia, in Endo World URO No. 17/5-D, 2000, pages 1 through 12. The main feature of this system is the D-LIGHT light system which is able to generate both white light and also fluorescence excitation light.
Usually such a system comprises the following: a viewing system, at least one light source, and a camera system for recording an image taken by the viewing system, the at least one light source being able to be operated in a first operating mode in which white light is generated, leading to a white light image, and the at least one light source being able to be operated in a second operating mode in which a first fluorescence excitation light of a first excitation wavelength range is generated, producing a fluorescence image in the visible range.
Endoscopic systems are used as the viewing system. However, it is also conceivable to use other viewing systems such as microscopic systems. It is furthermore possible for the viewing system and the camera system to be combined in one unit, for example in the form of a video endoscope.
Using such a system, the morphological structure of the surface of a hollow organ can be imaged and, with the aid of suitable tumor markers or the aforementioned autofluorescence, tumors can be distinguished with great contrast from normal tissue.
However, it is not possible to present certain functional properties of the tissue with this system. Among these functional properties, particular mention may be made of the perfusion of blood vessels.
The ability to view the perfusion would provide an operating surgeon with a further aid to distinguishing tumor tissue from surrounding healthy tissue. In addition, by the ability to view these functional properties of the tissue, the possible applications of such a system could be greatly extended, for example to check the status of tissue after transplantation, for example.
Methods for viewing the circulation of blood through a tissue are known per se. Thus, DE 694 33 413 T2 discloses a method in which a dye is injected into a patient's eye in order to view choroidal neovascularization, said dye filling the vascular structures of the eye. This dye can then be excited to fluorescence with the aid of excitation light in the range of the absorption maximum of the dye.
A dye used in this method and in related methods is indocyanine green (ICG). This dye has the structural formula shown below and has its absorption maximum at a wavelength of ca. 800 nm.

When ICG is excited to fluorescence by excitation light, it has a fluorescence maximum at ca. 840 nm. Both the absorption maximum and also the fluorescence maximum of ICG lie in the so-called near infrared range (NIR range). Since human tissue is relatively transparent in the NIR range, radiation in the NIR range can pass quite far through the tissue, and deeper-lying vessel structures can be made visible.
ICG also has the property of binding to proteins present in the blood plasma and, after its administration, does not pass out of the blood vessels and into the surrounding tissue to any great extent.
The object of the present invention is to make available a system with which it is possible to gather various kinds of information concerning the site that is to be viewed.